The formation and consolidation of memories requires bidirectional communication between the hippocampus and the neocortex via the entorhinal cortex (EC). EC layer V neurons are the main target of the processed output from the hippocampus and in turn project to cortical regions;these neurons are thus likely to play an important role in the formation and consolidation of memories. In addition, they have prominent apical dendrites that extend and branch in complex tufts in the EC superficial layers, where axons from different cortical areas are known to make synapses on EC layer II and III neurons. Our preliminary data show that these tufts carry many spines. The presence of these spines, combined with their proximity to axons emerging from cortical areas, suggests that these axons may form glutamatergic synaptic contacts on the distal dendrites of layer V neurons. The long-term goal of this research is to provide new insights with respect to the processing of memories by clarifying how entorhinal layer V neurons integrate the synaptic input they receive from the hippocampus with other inputs to generate their output to the neocortex. Two-photon Ca2+ imaging, glutamate uncaging and electrophysiological techniques will be employed to characterize different aspects of dendritic integration in layer V neurons of the rat entorhinal cortex. The project will focus on three specific aims: (1) to test the prediction that the distal apical dendrites of EC layer V neurons are activated by glutamatergic inputs whose features differ from those of the proximal hippocampal synapses;(2) to test the prediction that proximal and distal compartments can communicate through back-propagating action potentials (bAPs);(3) to test the prediction that the distal dendrites of EC layer V neurons can initiate dendritic spikes that alter the entorhinal output. The information acquired about the computational capabilities specific to the dendrites of these neurons will shed light on signal processing during normal and pathological neuronal activity. The resultant improvement in our understanding of how information is transmitted and stored in this critical area of the brain may eventually guide therapeutic strategies for disorders in which this area is particularly vulnerable, such as Alzheimer's disease, schizophrenia and epilepsy. PUBLIC HEALTH RELEVANCE: The formation and consolidation of memories requires bidirectional communication between the hippocampus and the neocortex via the entorhinal cortex. Two-photon Ca2+ imaging, glutamate uncaging and electrophysiological techniques will be used to characterize different aspects of dendritic integration in layer V neurons of the rat entorhinal cortex. The resultant improvement in our understanding of how information is transmitted and stored in this critical area of the brain may eventually lead to therapeutic strategies for disorders in which brain functions are compromised, such as epilepsy, Alzheimer's disease and schizophrenia.